Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation (TREAT-AF)

TRanscutaneous Electrical vAgus Nerve sTimulation to Suppress Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia. In previous experimental studies, the investigators found that low-level vagus nerve (VN) stimulation (LLVNS), at voltages substantially below that which slowed the sinus rate, significantly suppressed AF inducibility and decreased AF duration. The investigators subsequently developed a non-invasive neuromodulatory therapy, in which LLVNS was delivered to the auricular branch of the VN located at the tragus, the anterior protuberance of the outer canine ear (low level tragus stimulation; LLTS). The anti-arrhythmic effects of LLTS were similar to those of LLVNS delivered to the cervical VN trunk. More recently, in a proof-of-concept study in humans, the investigators showed that in patients with drug-refractory AF undergoing AF ablation, LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines.

The overall objective of this proposal is to translate in ambulatory patients with paroxysmal AF the results of previous studies showing acute suppression of AF and inflammation in anesthetized canines as well as humans, in order to examine the long-term therapeutic effects of this approach. The investigators hypothesize that intermittent (1 hour daily) LLTS for 6 months may result in long-term decrease of AF burden and suppression inflammatory cytokines in patients with paroxysmal AF. Patients will be randomized to either active or sham LLTS. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 1 hour daily over a 6-month period. AF burden will be defined as the percent of time spent in AF over a 2-week period, assessed by noninvasive continuous ECG monitoring at baseline and at 6 months. In addition, blood samples will be collected from patients at baseline, and at 3 and 6 months, for cytokine measurement. These investigations will establish the first evidence of the long-term effects of LLTS on AF suppression in patients with paroxysmal AF and may provide the basis for a potential expansion of the therapeutic targets of this treatment modality beyond AF.

Study Overview

• Status: Completed
• Conditions: Inflammation; Atrial Fibrillation
• Intervention / Treatment: Device: Parasym device

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients older than 21 year old
2. Paroxysmal AF

Exclusion Criteria:

1. Left ventricular dysfunction (Left ventricular ejection fraction <40%)
2. Significant valvular disorder (i.e., prosthetic valve or hemodynamically relevant valvular diseases)
3. Recent (<6 months) stroke or myocardial infarction
4. Severe heart failure (NYHA IV)
5. Left atrial dilatation (>55mm)
6. Recurrent vaso-vagal syncopal episodes
7. Unilateral or bilateral vagotomy
8. Pregnancy or breast feeding
9. Sick sinus syndrome, 2nd or 3rd degree AV block, bifascicular block or prolonged (PR>300ms) 1st degree AV block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Patients will receive 1 hour of active low level tragus stimulation daily for 6 months	Device: Parasym device
Sham Comparator: Sham; Patients will receive 1 hour of sham low level tragus stimulation daily for 6 months	Device: Parasym device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial Fibrillation Burden	Percent time spent in atrial fibrillation	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of Inflammation	Serum levels of tumor necrosis factor-alpha	6 months
Markers of Inflammation	Serum levels of inteleukin 6	6 months

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Stavros Stavrakis, MD, University of Oklahoma

Publications and helpful links

General Publications

• Stavrakis S, Stoner JA, Humphrey MB, Morris L, Filiberti A, Reynolds JC, Elkholey K, Javed I, Twidale N, Riha P, Varahan S, Scherlag BJ, Jackman WM, Dasari TW, Po SS. TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2020 Mar;6(3):282-291. doi: 10.1016/j.jacep.2019.11.008. Epub 2020 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: January 26, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: atrial fibrillation; inflammation; neuromodulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Inflammation; Atrial Fibrillation
• Other Study ID Numbers: RSRCH135160; 15MCPRP25790001 (Other Grant/Funding Number: American Heart Association)